The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel comprises four members (HCN1-4) that are expressed in the heart and nervous system — and while HCN4 is well understood to modulate heart rate and drive pacemaker activity, HCN2 has emerged as a promising target for pain management. To seize the potential of inhibiting the channel to relieve pain, Merck has tied up with King’s College London, hoping the collaboration will yield a potent new class of painkillers without the dangerous side-effects seen with prescription opioids.